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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
The orally bioavailable agent, MLN8237 (also known as alisertib), is a potent small-molecule inhibitor of Aurora A kinase (AAK) which is overexpressed in several types of tumor and associated with oncogenesis and tumor progression. It was developed from its predecessor, MLN8054, in order to minimize the benzodiazepine-like effects seen with MLN8054. The inhibitory effect of MLN8237 is ATP-competitive, reversible and AAK-specific with an inhibition constant (Ki) of 0.43 nmol/L. MLN8237 is being investigated to treat advanced malignancies, due to its both in vitro and in vivo activities against a broad range of tumor types.
Reference
E. Claire Dees, Roger B. Cohen, Margaret von Mehren, Thomas E. Stinchcombe, Hua Liu, Karthik Venkatakrishnan, Mark Manfredi, Howard Fingert, Howard A. Burris III, and Jeffrey R. Infante. Phase I study of aurora A kniase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Clin Cancer Res 2012; 18: 4775-4784.
Cell lines
TIB-48 and CRL-2396 cells
Preparation method
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reaction Conditions
>100 nM, 48 hours
Applications
TIB-48 and CRL-2396 cells were treated with MLN8237 at 10 nM, 50 nM, 100 nM, 500 nM and 1.0 μM for 48 h. MLN8237 induced apoptosis at concentrations >100 nM, suggesting that induction of apoptosis is dose-dependent. These results were confirmed by demonstrating an increased level of cleaved PARP in treated TIB-48 and CRL-2396 cells. PARP cleavage was observed even at the concentration of MLN8237 as low as 50 nM.
Animal models
Female C.B-17 SCID mice injected with OVCAR-5-pWZL-Luc cells
Dosage form
Oral administration, 20 or 30 mg/kg, once daily (QD) or twice daily (BID)
The mice (n=16/group) were randomly divided into five treatment groups: 1) vehicle, 2) 20 mg/kg alisertib, 3) 30 mg/kg alisertib, 4) 5 mg/kg paclitaxel and 5) 20 mg/kg alisertib + 5 mg/kg paclitaxel. Tumor growth was monitored by weekly BLI and the log-transformed total flux data showed significantly decreased tumor growth rates in mice treated with alisertib (20 or 30 mg/kg) compared to vehicle-treated mice. Treatment with 20 mg/kg and 30 mg/kg alisertib resulted in 51% and 49% TGI, respectively.
her notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1] Qi W, Spier C, Liu X, et al. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment. Leukemia research, 2013, 37 (4): 434-439.
[2] Do T V, Xiao F, Bickel L E, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene, 2013, 33 (5): 539-549.